lecture 2.gastric pathology 4.pdf

021 academic team Yousef abuwaar, Aya El Jaber, Sadeen Hindi  Pathology of the stomach-part 1 Manar Hajeer, md, FRCPath University of Jordan, School of medicine overview Gastric diseases: (acute gastritis, chronic gastritis ,acute 1-Inf...

021 academic team Yousef abuwaar, Aya El Jaber, Sadeen Hindi  Pathology of the stomach-part 1 Manar Hajeer, md, FRCPath University of Jordan, School of medicine overview Gastric diseases: (acute gastritis, chronic gastritis ,acute 1-Inflammatory. gastric ulcer and chronic peptic ulcers ) 2-Neoplastic. Normal anatomy & histology Before starting with pathology,. Let's start with normal anatomy and histology 4 mains parts : cardia, fundus, body, antrum(pylorus) Cardia: mucin secreting foveolar cells. These cells dominate the Cardia and they secrete mucin which protects and lines stomach from inside Body and fundus: contain specialized cells parietal cells (HCL) and chief cells (pepsin). Antrum: neuroendocrine G cells (gastrin) which stimulate the parietal cells to produce acid  Cardia is directly under the gastroesophageal junction. Then we have the Fundus Then the body which is the main part of the stomach. Then we have the Antrum which opens directly to gastroduodenal junction to duodenum. The histologic features of each part is different Each one had a different thickness  The Body and The Fundus : H&E stain Those pink cells are parietal cells that produces the acids Cardia of the stomach Body of the stomach Cardia region: The thickness is much less and all the top Antrum : It's cells are mucin more bluish in producing color because cells globular there's no epithelial parietal cells It has antrum type epithelia medcell.med.yale.edu Antrum of the stomach Inflammatory conditions Acute gastritis. Chronic gastritis. Acute gastric ulcer. Chronic peptic ulcer. ACUTE GASTRITIS and gastropathy ❖ Usually both are used interchangeably. Symptoms, presentation and pathogenesis are almost the same ❖ Acute Gastritis = inflammation , Gastropathy= there are changes but no inflammation or inflammatory cells Acute gastritis: Mucosal injury, neutrophils present. Acute= neutrophils, chronic=lymphocytes, plasma cells and macrophages Gastropathy: regenerative, no/rare inflammation. There is regeneration and damage but with NO inflammation at all Causes of gastropathy: NSAIDs, alcohol, bile, and stress-induced ❖ NSAID (the culprit)is the most common cause of Acute Gastritis. Clinical features: Asymptomatic sometimes the patient has a mild form of acute gastritis or gastropathy) , Epigastric pain , nausea, vomiting. Severe: erosions, ulcers, hematemesis, melena. Erosion=loss of the surface epithelium or ulcers which are more deep. Hematemesis is vomiting of blood. Melena is a black tarry colored stool due to upper GI bleeding. Pathogenesis Explanation in the next 2 slides It is long but trust me it will be easy Robbins Basic Pathology 10th edition Robbins Basic Pathology 10th edition  I) Usually pathogenesis of Acute and Chronic cases of Gastritis is the SAME. III) All these protective mechanisms work to counteract the normal damaging forces which are: 1. HCl, Gastric acidity 2. Peptic enzymes. II) In any injury we have damage and protective mechanisms. Example of protective mechanisms: 1-Surface Mucus secretion which acts as a barrier that prevent acidity from reaching cells. 2-The alkaline PH (by bicarbonate) that counteract the acidity(like a buffer) of the lumen of the stomach to protect the mucosa and lining of the lumen from getting damaged from the acidity of the stomach). 4-Mucosal blood flow: it's profuse(rich) are important for rapid regeneration of gastric mucosa also it buffers acidity(PH in stomach is 1 but in blood PH is 7) 5-Epithelial generative capacity which is produced but the mucosal blood flow and Prostaglandin synthesis 3-Prostaglandins especially PGI2 and E2 refer to slide 13 to learn about PDI2 and E2 Injurious stimuli 1-H.pylori infection 2-NSAIDs and Aspirin (it lowers PG) 3-Tobacco and Smoking 4-Alcohol 5-Gastric hyperacidity (anything that increase acidity is damaging (in general no acid = no ulcers)) 6-Duodenum gastric reflux If these injurious stimuli are Accompanied by impaired defensive mechanism due to ischemia, shock state, people taking COX inhibitors like NSAIDs which decrease PGs synthesis. Any imbalance between injurious stimuli and protective factors leads to ulceration and inflammation. This pathogenesis is the same for all inflammatory diseases acute and chronic but each disease has some special factors.  Pathogenesis of gastropathy, acute and chronic gastritis NSAIDs inhibits Imbalance between protective and damaging forces cyclooxygenase pathway thus inhibiting prostaglandins and thus inhibiting all Main causes: The main cause especially in acute gastritis is NSAIDs their protective mechanisms NSAIDs (COX1 and COX2 inhibitors) Uremic patients(chronic renal failure which has high ammonia levels) (ammonia inhibit bicarbonate transport(secretion)) H pylori produces urease enzyme which splits urea H pylori (urease produces ammonia) into ammonia and it inhibits bicarbonate secretion Aging (reduced mucin and bicarbonate secretion Bicarbonate secretion is compromised).Older people at a higher risk of acute and chronic inflammation Hypoxia (high altitudes) Harsh chemicals, (acids or bases) (direct epithelial injury) Direct mucosal injury(loss of epithelial cells) so we have an ulcer Alcohol, NSAIDs, radiation therapy (direct mucosal damage) NSAIDs do direct damage in addition to Chemotherapy (inhibit DNA synthesis and cellular renewal) decreasing PGs prostaglandins E2 and I2: Stimulate nearly all of the defense mechanisms including 1-Mucus and bicarbonate secretion, 2-increase mucosal blood flow 3-Epithelial restitution.(regeneration) MORPHOLOGY 1- endoscopy or colonoscopy = macroscopic 2-Biobsy = Microscopic Hyperemia.(redness)(erythema) (macroscopic) Red color appearance and could be accompanied by hemorrhage in severe cases Edema and slight vascular congestion seen under the microscope Neutrophils, lymphocytes, and plasma cells are not prominent. Neutrophils : Active inflammation (gastritis).(Not seen in gastropathy) Intact surface epithelium if mild.(In mild forms of acute gastritis and gastropathy) Acute erosive hemorrhagic gastritis (Advanced)  This is the erythema or redness. Usually, gastric mucosa is light brown When redness is seen in endoscopy we know it's inflammation Redness is due to vascular congestion in lamina propria www.etttamen.com  This is under the microscope Note: Doctor said that in the exam microscopic pictures and not important but macroscopic pictures are important These red spots are RBCs represent hemorrhage This is hemorrhagic gastritis These white spots are edema Stress-Related Mucosal Disease acute gastric ulcers Acute gastritis Severe physiologic stress: MAINLY complicated with Acute Gastric Ulcers usually are associated with physiological stress ulcers Trauma Extensive burns Intracranial disease Major surgery Serious medical disease Critically ill patients Next slide And the type of ulcer is usually related to one type of stress Acute gastric ulcers: Stress ulcers: critically ill patients with shock (which causes decrease diffusion to organs like stomach, since the blood flow decreased so by this we would have lost a protective factor) , sepsis, or severe trauma. Curling ulcers: proximal duodenum , commonly caused by severe burns or trauma. Cushing ulcers: stomach, duodenum, or esophagus, CNS injury as stroke, high risk of perforation. (elevated intracranial pressure (because of a brain tumor for example) cause vagal stimulation which increases acid production and leads to ulcer)  Mostly due to local ischemia ( decreased Pathogenesis blood flow) Stress ulcers: Mostly due to Local ischemia by. (like in shock state) Systemic hypotension. (lowers blood diffusion in stomach) Decreased blood flow (Splanchnic vasoconstriction) (vasoconstriction of arteries supplying the GI tract) Systemic acidosis (lower intracellular PH). COX2 expression is protective. (so PG will still be produced and the protective mechanisms of PG will be existing and not changed) CNS injury and Cushing ulcers: The vagus nerve is the main stimulator of acid secretion Direct vagal stimulation, acid hypersecretion. because part of the parasympathetic system  MORPHOLOGY Spectrum (Shallow to deep). Acute ulcers are rounded and typically < 1 cm. Ulcer base brown to black. Multiple, anywhere in stomach Normal adjacent mucosa No scarring because acute Healing with complete epithelialization occurs days or weeks after removal of injurious factors In acute ulcer, the body heal itself WITHOUT any intervention from us, we only heal the cause, for example the shock BUT when the blood flow return to the stomach, regeneration (reepitheliazation) happen by the body itself, and so the ulcer disappears heal WITHOUT scaring unlike the chronic ulcer  The usual scenario: A patient is depleted in the ICU, starts by nausea, vomiting and could vomit blood (hematemesis or melena) (upper GI bleeding) When we do endoscopy: -We have MULTIPLE gastric ulcers(acute) not only one(chronic). Appear as multiple small pinpoint distributed over the surface. - Base of ulcer black or brown due to the blood staining of the ulcer caused by gastric acidity - Mucosa between ulcers are NORMAL, no inflammation or gastritis in between. Not considered gastritis that transformed to ulcer, but they are stress ulcer from the beginning due to the physiological stress  Clinical features Acute epigastric pain Nausea, vomiting, Melena (black stool, strong indicator for upper GI bleeding) Coffee -ground hematemesis Think about it for a minute :Why coffee- ground color?? Perforation complication. The action of pepsin and acids in the stomach on the blood from bleeding, turn the blood from red Prophylaxis with proton pump inhibitors to brownish. Outcome depends on severity of underlying cause. ❑ Coffee-ground hematemesis OR melena indicate upper GI bleeding (stomach/esophagus). ❑ Acute gastric ulcer and stress ulcer carry risk of perforation, and so the most important action taken in this case: PROPHYLAXIS. Moreover, patients in ICU or after major surgery, it’s very important to provide prophylaxis with PPI to decrease acidity and prevent ulcers. ❑ The outcome in these cases depend on the underlying causes severity (mild/severe perforation), since the acute gastric ulcer from NSAIDs is different from stress ulcer from being critically ill and ICU, and so the outcome differ  CHRONIC GASTRITIS : gradual less severe onset, over a long period of time, but remember that in contrast acute gastritis has rapid onset and happens over a short period of time. (Similar pathogenesis) Causes: (MAIN CAUSES) 1. Helicobacter pylori associated gastritis: most common. (gram negative bacteria responsible for 75% of cases) 2. Autoimmune atrophic gastritis: less than 10% of cases. The rule here: 3. Less common causes ALWAYS diagnose chronic gastritis cause as H.pylori UNTIL proven otherwise Chronic NSAID (NSAIDS usually associated with ACUTE gastritis, but it could be chronic however less commonly) Radiation injury Depending also on the state, some of them different percentages: in the USA the NSAIDs are more Chronic bile reflux. (From duodenum to the stomach) common that the H.pylori, because the bacteria is dropping while the NSAIDs use among the older age population is increasing  Clinical features Remember all types of gastritis including acute and chronic present with epigastric pain, nausea and vomiting however chronic patients have symptoms over a long period of time Nausea and upper-abdominal discomfort Vomiting Hematemesis uncommon (occur in some cases). (Autoimmune and H.pylori present the same so the clinical features alone can't differentiate them) Less severe but more prolonged symptoms.  Helicobacter pylori Gastritis Discovery of the association of H.pylori with peptic ulcer disease was a revolution. (Since the gastritis was a very common patient complaint, so solving it by antibiotics (triple therapy) for H.pylori was a revolution) (peptic ulcer: any ulcer in an area of GI tract) Spiral or curved, G-ve, bacilli. In almost all duodenal ulcers and majority of gastric ulcers or chronic gastritis. (since it’s surely from the acid hypersecretion in the stomach which then go to duodenum caused by H.pylori, unlike gastric ulcers which can be caused by other various causes mentioned in the previous slide) So when the doctor use endoscopy and notice duodenal ulcer, it’s for sure H.pylori. If he noticed gastric ulcer, then he should take a biopsy to know when cause from what mentioned is the one.  Helicobacter pylori Gastritis Epidemiology: Poverty, poor sanitation. Acquired in childhood, persists to adult-life. Acute infection is subclinical. (acute infection or acquisition goes unnoticed but the infection persist making it chronic with symptoms, but there is some patients who has acute infection and bacteria persist there without causing symptoms in the future) (subclinical: unnoticed) How do they live in the stomach? lives extracellular around the mucosa covering specially in antrum causing antral gastritis Pathogenesis: Non-invasive, adapted to live in the mucus layer, non-invasive(do not enter cell), by Flagella: allow motility. Urease: split urea to ammonia, protect bacteria from acidic pH. (by surrounding themselves with basic environment) Adhesins: bacterial adherence to foveolar cells (gastric mucosa) Toxins: (CagA) mucosal damage  Slide from 021 Majority of gastric ulcers or chronic gastritis. Antral gastritis with increased acid production >> peptic ulcer (H.pylori like to colonize the antrum of the stomach, which leads to the characteristic duodenal ulcers because the duodenum receives a lot of acid) Severe cases: Pangastritis if severe with hypochlorhydria (hypochlorohydria due to reduced parietal cell mass and secretion) (pangastritis: inflammation affecting all of the stomach) Intestinal metaplasia and increased risk of gastric cancer. Most feared matter in chronic gastritis is Intestinal metaplasia in the stomach because it can progress to dysplasia to gastric adenocarcinoma ( it’s most cases is caused by H.pylori !!!) Pathogenesis Most important complication is: Starts as Antral If severe: spread to gastritis >>stimulate G Intestinal metaplasia body with atrophy cells >> increased acid and increased risk of (damage Parietal production >> peptic gastric cancer. cells). ulcer Starts in the antrum, causing antral gastritis Presence of goblet cells in the Stimulates G cells that produces gastrin and stomach (where they shouldn't increases acid production be) h.pylori is a bacteria that is able to protect itself Metaplasia> dysplasia> cancer from the surrounding environment, and in the meantime it increases the body's acid secretion causing peptic ulcer in the long run MORPHOLOGY Gastric biopsy (golds standard to visualize the gastric biopsy under microscope) : H. pylori in mucus layer, antrum. We can see them on H&E stain or special type of stain like giemsa stain , silver stain Regenerative changes (hyperplastic polyps) Neutrophil, plasma cells, lymphocytes & macrophages. Lymphoid aggregates>>> increased risk of MALT lymphoma. Intestinal metaplasia (goblet cells)>>> dysplasia >> increased risk of adenocarcinoma ❑As a pathologist: You would try searching for H.pylori in the antrum SURFACE not inside cells, since it prefers antrum region. ❑If there was a chronic inflammation, we would find lymphocytes ,macrophages and plasma cells. ❑If there was ACTIVE CHRONIC , there would be neutrophils also ❑If lymphoid aggregation is exaggerated and prolonged to be too severe may lead to predispose MALT lymphoma associated with bone. ❑ If intestinal metaplasia isn’t treated, it would be predisposed to dysplasia and then adenocarcinoma. Intestinal metaplasia: is indicated by the presence of goblet cells in the stomach even though goblet cells aren’t supposed to be found there. Recap: ❑H.Pylori can cause 2 cancers: 1-MALT Lymphoma 2-Gastric adenocarcinoma  Here we have a lot of NEUTROPHILS attacking the epithelium , this is an ACTIVE chronic Epithelium surface H&E stain Lymphoid aggregates ,a lot of plasma cells and lymphocytes above The rod black color bacteria (H.pylori) are many in here. The stain used here is silver stain. Robbins Basic Pathology 10th edition Intestinal metaplasia the clue for detecting metaplasia is goblet cells as we are not supposed to see goblet cells in the stomach because its an intestinal type of cell. Robbins Basic Pathology 10th edition  Diagnosis and treatment Diagnosis of H. pylori gastritis depends on: History (patient with Serologic test: anti-H.pylori antibodies. epigastric pain, nausea, vomiting...) Stool test for H.pylori Physical (testing for the antigen [bacteria is there]; this is better than examination/investigation antibody testing as it could be indicating a previous infection ) which include: ✓ invasive methods (like biopsy Urea breath test. (not that much used instead we use rapid urease & endoscopy ) test during endoscopy) ✓ noninvasive methods (like taking a blood sample , test (Above are the non-invasive diagnostic methods now we will talk antibodies for H.pylori or about the invasive methods below) stool sample for H.pylori Gastric antral biopsy (The gold standard ) (rapid urease test during antigens) endoscopy) Bacterial culture. (not that much used) PCR test for bacterial DNA. (not that much used) Treatment: combinations of antibiotics and PPI (triple therapy). (2 antibiotics with PPI taken on long duration to eradicate H.pylori)  Autoimmune Gastritis (10% of chronic gastritis) ❖ Another reason for chronic gastritis is autoimmune gastritis. From its name we can deduce that there are antibodies attacking body cells (parietal cells in this case). ❖ Parietal cells produce acid, so loss of parietal cells will lead to hypo-acidity (unlike in H. pylori gastritis > hyperacidity). Antibodies to parietal cells and intrinsic factor in serum. (Intrinsic factor is important in absorption of vitamin B12 Reduced serum pepsinogen I levels (since these antibodies could also attack chief cells) Antral endocrine cell hyperplasia due to decrease in acidity--> G cells would proliferate --> with time, gastrin-producing cell undergo hyperplasia to increase acid production ,but it doesn’t increase because there’s no parietal cells the cycle continues ( closed circle). These patients are at risk to develop neuroendocrine tumors from the proliferation of G cells. Vitamin B12 deficiency >>> pernicious anemia and neurologic changes Impaired gastric acid secretion (achlorhydria) Marked hypergastrinemia In contrast h.pylori affect the antrum while autoimmunity affects Spares the antrum. parietal cells in the body  Pathogenesis Immune-mediated loss of parietal cells >>> reductions in acid and intrinsic factor secretion. Acid reduction >>hyperplasia of antral G cells (which produce gastrin)>>hypergastrinemia Deficient intrinsic factor >> deficient ileal VB12 absorption >> pernicious anemia.  MORPHOLOGY Damage of the oxyntic (acid-producing) mucosa. (Oxyntic because cytoplasm of parietal cells is pink) Diffuse atrophy, thinning of wall, loss of gastric folds (that's why it's sometimes called atrophic gastritis) Lymphocytes, plasma cells, macrophages, less likely neutrophils. (chronic inflammation) Intestinal metaplasiac >>> dysplasia >> carcinoma. G-cell hyperplasia >>> carcinoids. Neuroendocrine (g cells) cell hyperplasia >>> tumors. Clinical features 60 years, slight female predominance. Often associated with other autoimmune diseases (most autoimmune diseases has slight female predominance and they tend to cluster together) Dyspepsia. (Clinical description to the upper abdominal discomfort ,nausea and vomiting). Anemia (VB12 or iron) ✓ This table is very important. It summarizes everything we've mentioned (differences between H. pylori gastritis and autoimmune gastritis). (After effect) Carcinoid tumor:Neuroendocrine cells tumor Robbins Basic Pathology 10th edition Adenocarcinoma are due to intestinal metaplasia Complications of chronic gastritis Peptic ulcer. Mucosal atrophy. Intestinal Metaplasia Dysplasia.